期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 88, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.intimp.2020.106949
关键词
Network pharmacology; Dihydroartemisinin; Colitis; NLRP3 inflammasome; p38 MAPK
资金
- National Natural Science Foundation of China [81873143]
- Double-Hundred Talent Plan of Shanghai Jiao Tong University School of Medicine [20191831]
Dihydroartemisinin (DHA), a sesquiterpene lactone derived from artemisinin, has been reported to possess anti-inflammation and anti-cancer activities. But its underlying protective mechanisms on dextran sodium sulphate (DSS)-induced colitis remain rarely reported. We applied a network pharmacology approach to predict the collective targets of DHA and acute colitis. GO and KEGG analyses were performed to investigate the enriched biological functions and signaling pathways of the collective targets. Furthermore, a DSS-induced colitis model was established to observe the protective effects of DHA. 83 common targets of DHA and acute colitis were identified and predominantly involved in several inflammation-related signaling pathways in colitis such as NOD-like receptor and MAPK signaling pathways. Additionally, DHA in vivo improved the clinical symptoms, reduced the production of pro-inflammatory factors IL-1 beta, IL-6 and TNF-alpha, and suppressed the formation of NLRP3 inflammasome. Moreover, DHA inhibited the phosphorylation of NF-kappa B p65 and p38 MAPK, but upregulated PPAR gamma and Ki-67 levels compared to the DSS group. Additionally, we found that DHA suppressed p38 activator-induced pro-inflammatory response, and p38 inhibitor attenuated the clinical symptoms and reduced the expression levels of pro-inflammatory mediators and NLRP3 while up-regulated the expression levels of PPAR gamma and Ki-67. Molecular docking analysis further verified the binding mode towards the DHA and p38 MAPK. In conclusion, DHA could protect DSS-induced colitis via suppressing the activation of NLRP3 inflammasome and p38 MAPK signaling.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据